The biology of the extracellular matrix: novel insights.
The biology of the extracellular matrix: novel insights.
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DOI：
10.1097/bor.0b013e32835b137b
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发表时间：
2013-01
影响因子：
5.1
通讯作者：
Apte SS
中科院分区：
文献类型：
--
作者：
Hubmacher D;Apte SS
细胞外基质（ECM）具有结构和调节作用。本更新回顾了ECM生物学与炎症、组织破坏、纤维化和再生相关的各个方面的代表性最新进展。ECM的生物调节正在成为一个主要的研究领域，由几个新的方向驱动。发现ECM提供的机械信号的感测在调节细胞分化中至关重要。转化生长因子-β（TGF-β）是纤维化和炎症的关键因子。结构生物学和细胞生物学的结合为细胞牵引和ECM激活其机制提供了新的见解。通过分析以TGF-β失调为潜在病理机制的遗传性结缔组织疾病，提高了对微纤维中的纤维蛋白和相关蛋白如何调节TGF-β螯合和活化的理解。对microRNA介导的ECM调节的见解表明miR-29的关键作用，其潜在的治疗作用正在出现。了解蛋白酶对细胞外基质代谢的进展为细胞调节提供了新的见解，并确定了有用的疾病生物标志物。作为细胞行为的重要调节剂，ECM对人类疾病具有非常强的相关性和翻译意义，为疾病发病机制的理解以及治疗开辟了新的机会。
Extracellular matrix (ECM) has both structural and regulatory roles. This update reviews the representative recent developments in diverse aspects of ECM biology relevant to inflammation, tissue destruction, fibrosis, and regeneration. Biological regulation by ECM is emerging as a major research area, driven by several new directions. Sensing of mechanical cues provided by ECM was found to be crucial in regulating cell differentiation. Transforming growth factor-β (TGF-β) is a pivotal agent in fibrosis and inflammation. A combination of structural biology and cell biology provided novel insights on the mechanisms of its activation by cellular traction and ECM. Improved understanding of how fibrillin microfibrils and associated proteins regulated TGF-β sequestration and activation was achieved by analysis of inherited connective tissue disorders having TGF-β dysregulation as an underlying pathologic mechanism. Insights on microRNA-mediated ECM regulation suggest a key role for miR-29, for which potential therapeutic roles are emerging. Advances in understanding the ECM turnover by proteinases provided novel insights on cell regulation and identified useful disease biomarkers. As a crucial modulator of cell behavior, ECM has exceptionally strong relevance and translational implications for human disease, opening novel opportunities for mechanistic understanding of disease pathogenesis as well as treatment.